Clozapine, can be poorly tolerated, with several unpleasant side effects and adverse drug reactions (ADRs) needing regular monitoring. Because of this it is difficult to deliver clozapine to treatment-resistant patients who may need it. Improvements in therapeutic drug monitoring and overall safety of clozapine, for example by reducing the risk of ADRs or more effective therapeutic concentration, could reduce the number of patients either refusing clozapine therapy, or reduce treatment failure either because of lack of efficacy or ADRs. The development of treatment resistance should be avoided if possible, and this might also be achieved by giving clozapine to patients much sooner in their illness.

The most notorious ADR is agranulocytosis (loos of white blood cells), which has proved fatal in a few individuals. Because of this, the use of clozapine in the UK and most other countries is confined to treatment-resistant cases, with regular monitoring.

The landmark study by Kane et al. (1988) demonstrated the efficacy of clozapine in treatment-resistant patients as well as its safety, provided the patient’s white cell count was monitored and led to the reintroduction of the drug to the US market in the early 1990s and shortly thereafter in to the UK market.